The overall objective of this proposal is to characterize marrow-dependent (M) cells. We will test the hypothesis that Natural Killer (NK) cells reactive against YAC-1 lymphoma cells are M cells. We will utilize 89Sr-treated mice in which the NK(YAC) activity is lowered, presumably due to chronic irradiation and destruction of bone marrow microenvironment. Reconstitution of NK(YAC) function in 89Sr-treated mice will be attempted by implantation of normal bone or bone marrow plugs. Low NK(YAC) activity in 89Sr-treated mice is not stimulated by interferons. We will investigate the basis of interferon unresponsiveness by studying interferon binding by NK cells. The role of marrow-independent and marrow dependent NK cells in tumor cell lysis in vitro and protection against tumors in vivo will be investigated. This will be done by purifying various NK cells following absorption over tumor cell monolayers. The role of Hemopoietic histocompatibility (Hh) antigens as target structures for NK cells will be investigated by evaluating the association of susceptibility to NK mediated lysis and expression of Hh antigens. The regulation of suppressor cells by M cells will be ascertained by investigating the possible suppressor cell function of normal thymocytes which are susceptible to lysis by NK(YAC) cells.